Arylsulfatases A and B, shown to be elevated in human osteoarthritic articular cartilage, were isolated and purified from this tissue. The physiological roles of these enzymes in articular cartilage will be determined and factors which influence the de novo synthesis and the regulation of their activities in normal and pathologic tissues will be examined. The enzymes will also be isolated and purified from chondrocytes grown in culture. The properties of these enzymes will be compared with those from the intact tissue. We propose to identify, isolate and purify the enzymes responsible for the desulfation of chondroitin and keratan sulfates, the principal glycosaminoglycan components in adult human articular cartilage. A possible relationship of these enzymes to the purified arylsulfatases will be characterized and compared with those described for other tissues. If, as has been shown for the latter, the substrates are also oligosaccaride sulfates, the presence of a "chondroitinase" type of enzyme, reported to be present in epiphyseal cartilage, will be sought in human articular cartilage. Chondrocyte culture systems established from normal and osteoarthritic human articular cartilage will be employed to examine and compare the effects of Vitamin C, hyaluronic acid, insulin, and factors isolated from normal and osteoarthritic human sera and synovial fluid on sulfated proteoglycan and collagen metabolism. In the broadest sense, this research is directed toward a better understanding of the regulation of proteoglycan and collagen metabolism under different physiological conditions with a view to facilitating early diagnosis and providing a rationale for non-surgical therapy in osteoarthritis.